Hemodynamics and Vascular Histology of Keloid Tissues and Anatomy of Nearby Blood Vessels.

Keloids are red' invasive scars that are driven by chronic inflammation in the reticular dermis. The role of blood vessels in keloid behavior remains poorly understood. In the present study with 32 keloid patients, we examined the hemodynamics of keloid tissue, the anatomy of the blood vessels feeding and draining the keloids, and the vascular histology of keloids. Methods: Ten patients with large anterior chest keloids underwent near-infrared spectroscopy, which measured regional saturation of oxygen and total hemoglobin index in the keloid and surrounding skin. Another 10 patients with large chest keloids and three healthy volunteers underwent multidetector-low computed tomography. The extirpated chest keloids of 12 patients were subjected to histology with optical, CD31 immunohistochemical, and electron microscopy. Results: All keloids had a low regional saturation of oxygen and a high total hemoglobin index, which is indicative of blood congestion. Multidetector-low computed tomography revealed dilation of the arteries and veins that were respectively feeding and draining the keloid leading edge. Hematoxylin-eosin staining and CD31 immunohistochemisty revealed considerable neovascularization in the keloid leading edge but not in the center. Electron microscopy showed that the lumens of many vessels in the keloid center appeared to be occluded or narrowed. Conclusions: Keloids seem to be congested because of increased neovascularization and arterial inflow at the leading edge and blocked outflow due to vascular destruction in the center. The surrounding veins seem to expand in response to this congested state. Methods that improve the blood circulation in keloids may be effective therapies.

Efficacy and Safety of the Cholesteryl Ester Transfer Protein Inhibitor Evacetrapib in Combination With Atorvastatin in Japanese Patients With Primary Hypercholesterolemia.

BACKGROUND: Inhibition of cholesteryl ester transfer protein by evacetrapib when added to atorvastatin may provide an additional treatment option for patients who do not reach their low-density lipoprotein cholesterol (LDL-C) goal.Methods and Results:This multicenter, randomized, 12-week, double-blind, parallel-group, placebo-controlled, outpatient, phase 3 study evaluated the efficacy of evacetrapib with atorvastatin in reducing LDL-C in 149 Japanese patients (evacetrapib/atorvastatin, n=53; ezetimibe/atorvastatin, n=50; placebo/atorvastatin, n=46) with primary hypercholesterolemia. The primary efficacy measure was percent change from baseline to week 12 in LDL-C (ß quantification). Treatment with evacetrapib 130 mg daily for 12 weeks resulted in a statistically significant treatment difference of -25.70% compared with placebo in percentage decrease in LDL-C (95% CI: -34.73 to -16.68; P<0.001). Treatment with evacetrapib 130 mg also resulted in a statistically significant difference of 126.39% in the change in high-density lipoprotein cholesterol (HDL-C) compared with placebo (95% CI: 113.54-139.24; P<0.001). No deaths or serious adverse events were reported. Four patients (3 in the evacetrapib group and 1 in the ezetimibe group) discontinued due to adverse events. CONCLUSIONS: Evacetrapib daily in combination with atorvastatin was superior to placebo in lowering LDL-C after 12 weeks, and resulted in a statistically significant increase of HDL-C compared with placebo. Also, no new safety risks were identified.

Efficacy and Safety of Cholesteryl Ester Transfer Protein Inhibitor Evacetrapib Administered as Monotherapy in Japanese Patients With Primary Hypercholesterolemia.

BACKGROUND: Inhibition of cholesteryl ester transfer protein with evacetrapib may provide an additional treatment option for patients who do not reach their low-density lipoprotein cholesterol (LDL-C) goal with statins or patients who cannot tolerate statins.Methods and Results:This multicenter, randomized, 12-week, double-blind, parallel group, placebo-controlled, outpatient, phase 3 study evaluated the efficacy of evacetrapib in reducing LDL-C in 54 Japanese patients (27 evacetrapib, 27 placebo) with primary hypercholesterolemia. Primary efficacy measure was the percent change from baseline to week 12 in LDL-C (ß quantification). Treatment with evacetrapib 130 mg once daily for 12 weeks resulted in statistically significant (P<0.001) change in LDL-C (ß quantification) compared with placebo. Least-squares mean percentage changes from baseline were -34.3% in the evacetrapib group vs. 0.0% in the placebo group. Treatment with evacetrapib 130 mg also resulted in a statistically significant (P<0.001) increase in high-density lipoprotein cholesterol compared with placebo in mean percent change from baseline, with a least-squares mean difference of 124.0% (95% confidence interval: 104.6-143.5). No deaths, serious adverse events, or discontinuations because of adverse events were reported; 5 patients (18.5%) in the evacetrapib group and 7 patients (26.9%) in the placebo group experienced treatment-emergent adverse events. CONCLUSIONS: Once-daily evacetrapib 130 mg monotherapy was superior to placebo in lowering LDL-C after 12 weeks. No new safety risks were identified.

Reconstruction after Anterior Chest Wall Keloid Resection Using Internal Mammary Artery Perforator Propeller Flaps.

It is difficult to completely resect huge anterior chest wall keloids and then close the wound directly. We report here our retrospective analysis of our case series of patients with such keloids who underwent reconstruction with internal mammary artery perforator (IMAP) pedicled propeller flaps and then received postoperative high-dose-rate superficial brachytherapy. METHODS: All consecutive patients with large/severe keloids on the anterior chest wall who underwent keloid resection followed by reconstruction with IMAP-pedicled propeller flaps and then high-dose-rate superficial brachytherapy in our academic hospital were identified. All cases were followed for >18 months. Donor site position, perforator pedicle, flap size, angle of flap rotation, complications, and recurrence were documented. RESULTS: There were nine men and one woman. The average age was 37.9 years. The average follow-up duration was 28.7 months. The largest flap was 16 × 4 cm. The dominant perforators of the internal mammary artery were located in the sixth (n = 2), seventh (n = 5), eighth (n = 1), and ninth (n = 2) intercostal spaces. Twelve months after surgery, patients reported marked relief from keloid-associated pain and itching, except in two patients who underwent partial keloid resection; their remaining keloids were still troublesome but after conservative therapies, including steroid ointments/plasters, the keloids gradually ameliorated. Eighteen months after surgery, there was no keloid recurrence or new development of keloids on the donor site. CONCLUSIONS: IMAP-pedicled propeller flaps transfer skin tension from the anterior chest wall to the abdomen. Our series suggests that this approach combined with radiation therapy can control keloid recurrence.

Estimating Lymphodynamic Conditions and Lymphovenous Anastomosis Efficacy Using (99m)Tc-phytate Lymphoscintigraphy with SPECT-CT in Patients with Lower-limb Lymphedema.

BACKGROUND: Diagnostic and therapeutic strategies for lower-limb lymphedema have not yet been established. The purpose of this study was to estimate the lymphodynamic condition and therapeutic efficacy of lymphovenous anastomosis (LVA) in lower-limb lymphedema patients using 2-phase (99m)Tc-phytate lymphoscintigraphy with single-photon emission computed tomography-computed tomography (SPECT-CT). METHODS: In this study, consecutive patients with lower-limb lymphedema who underwent 2-phase lymphoscintigraphy using (99m)Tc-phytate were enrolled between June 2013 and June 2014. SPECT-CT was also performed to clarify the relationships between functional and morphological information. In both the early and delayed images, inguinal lymph node accumulation, dermal backflow, and their sequential alternations were evaluated, and liver-to-blood ratio and inguinal lymph node-to-blood ratio were calculated. All participants were classified into 6 types of lymphodynamic conditions based on the image findings. Patients with both dermal backflow and associated normal lymphatic vessel accumulation proceeded to LVA and underwent a second lymphoscintigraphy after the operation. RESULTS: Of all 30 participants, the largest population was categorized as type 4, which had consistent inguinal lymph node accumulation defect with dermal backflow. In 12 operated cases, dermal backflow was degraded in 10 cases by LVA. Liver-to-blood ratio in both early and delayed images and inguinal lymph node-to-blood ratio in delayed image significantly increased after LVA. CONCLUSIONS: Lymphoscintigraphy with SPECT-CT can provide both functional and morphological information simultaneously in patients with lower-limb lymphedema. Using these procedures, a type categorization for the patients was devised, which reflects their lymphodynamic conditions. The therapeutic efficacy of LVA could also be estimated quantitatively by the derived findings.

Cardio-oncology/onco-cardiology.

An understanding of onco-cardiology or cardio-oncology is critical for the effective care of cancer patients. Virtually all antineoplastic agents are associated with cardiotoxicity, which can be divided into 5 categories: direct cytotoxic effects of chemotherapy and associated cardiac systolic dysfunction, cardiac ischemia, arrhythmias, pericarditis, and chemotherapy-induced repolarization abnormalities. Radiation therapy can also lead to coronary artery disease and fibrotic changes to the valves, pericardium, and myocardium. All patients being considered for chemotherapy, especially those who have prior cardiac history, should undergo detailed cardiovascular evaluation to optimize the treatment. Serial assessment of left ventricular systolic function and cardiac biomarkers might also be considered in selected patient populations. Cardiotoxic effects of chemotherapy might be decreased by the concurrent use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta-blockers. Antiplatelet or anticoagulation therapy might be considered in patients with a potential hypercoagulable state associated with chemotherapy or cancer. Open dialogue between both cardiologists and oncologists will be required for optimal patient care.